Journal Article

Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients

Storch, Gregory A., Brennan, Daniel C., Viscidi, Raphael P., Pastrana, Diana V., Randhawa, Parmjeet S., Buck, Christopher B., Çuburu, Nicolas

2012

Overview

BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Antibodies, Neutralizing - blood / Antibodies, Neutralizing - immunology / Antibodies, Neutralizing - pharmacology / Antibodies, Viral / Biology / BK Virus - immunology / BK Virus - metabolism / Disease Models, Animal / Female / Genetic aspects / Genotype / Genotypes / Health aspects / Humans / Immunization / Infections / Kidney Diseases - immunology / Kidney Diseases - prevention & control / Kidney Transplantation / Kidneys / Male / Medical research / Medicine / Mice / Mice, Inbred BALB C / Neutralization / Physiological aspects / Polyoma virus / Polyomavirus Infections - blood / Polyomavirus Infections - immunology / Polyomavirus Infections - prevention & control / Time Factors / Transplantation / Transplants & implants / Vaccination - methods / Viral genetics / Viral Vaccines - immunology / Viral Vaccines - pharmacology / Virulence (Microbiology)